Mass spectrometry is an analytical methodology used for qualitative and quantitative determination of compounds in chemical and biological samples. Analytes in a sample are ionized, separated according to their mass by a spectrometer and detected to produce a mass spectrum. The mass spectrum provides information about the masses and in some cases the quantities of the various analytes that make up the sample. In particular embodiments, mass spectrometry can be used to determine the molecular weight or the molecular structure of an analyte in a sample. Because mass spectrometry is fast, specific and sensitive, mass spectrometer devices have been widely used for the rapid identification and characterization of biological analytes.
During the last few years, matrix-based ionization methods, e.g., matrix-assisted laser desorption/ionization (MALDI) methods have proven to be valuable for the ionization of samples, and have found widespread use in a variety of fields such as genomics and proteomics. In performing matrix-based methods, a sample is combined with an organic matrix that co-crystallizes with the sample, and then deposited upon a sample plate. The sample plate is placed in an ion source, and an energy source, e.g., a laser beam vaporizes the sample. During vaporization of the sample, analyte ions are formed. It is thought that the presence of the matrix enables the analyte to be ionized, solving a problem of other methods.
In many cases, matrix-based ion sources are integrated with an analytical device, e.g., a mass spectrometer, for studying the ionized analyte. For the most part, time-of-flight mass spectrometers (“TOF-MS”) are used for this purpose, however a variety of other mass spectrometers may also be used, including an ion cyclotron resonance spectrometer (e.g., a Fourier transform ion cyclotron mass resonance spectrometer), an ion trap mass spectrometer (e.g., a high-frequency quadrupole ion trap mass spectrometer), or a hybrid instrument (e.g., a quadrupole/time-of-flight mass spectrometer, or Q-TOF).
In ionizing a sample using matrix-based ionization methods, it is generally desirable to view an area on a sample plate to ensure that a sample has been deposited onto that area, and to ensure that the laser is actually going to impact the sample. In particular, there is a need for an imaging system that provides a detailed image of the sample, in particular an image that shows areas of analyte crystals.
Prior art imaging systems are capable of capturing an image of a sample on a sample plate for a matrix-based ion source, and transferring such an image to a monitor so that the sample can be viewed. However, because of the optics employed in those imaging systems, they are generally limited because they do not produce a high resolution, high contrast image that is in-focus over the entire field of view, or at least an extended area of field of view.
For example, the production of a high resolution image of an area of a sample plate in a matrix-based ion source is challenging because, in general, the area cannot be viewed directly from above (i.e., from the z direction when the x and y directions are coplanar with the surface of the sample plate). In most cases, in producing an image of an area of a sample plate in a ion source, the area must be viewed from the side, at an angle that can vary greatly depending on the particular ion source and imaging system used. The production of a high resolution image using such a system is challenging because of limitations that are inherent to the imaging systems used.
A need still exits, therefore, for a new matrix-based sample plate imaging system. The present invention meets this need, and others.